The medical and economic benefits to be gained from improved or enhanced wound healing therapies are obvious. Hence, new methods and processes for promoting wound healing have been continuously pursued, especially for chronic, indolent wounds, which can be a frustrating aspect of patient care.
While high-powered lasers have been accepted and used successfully in a variety of clinical settings, only rarely have low-power lasers been used or even investigated. The clinical applications of low-power continuous wave or pulsed emission lasers operating in the mW range may be potentially extensive. The low-power laser may be especially effective in treating superficial wounds and musculoskeletal disease or injury. Basford, "Low-Energy Laser Treatment of Pain and Wounds: Hype, Hope or Hokum?" Mayo Clin. Proc. 61:671-75, 1986, in an editorial critique, reported that "although the substantiation of results has varied greatly in detail and quality, many investigators have described successful treatment of a wide variety of painful musculoskeletal, rheumatologic, and neurologic conditions with low-energy lasers." Such effects of low-power or low-energy lasers are referred to as biostimulation.
Some studies of wound healing have found a "systemic effect" from laser treatment. Pain and inflammation have decreased and healing has improved at sites distant from the treated areas. These observations may be supported by a report of increased excretion of urinary 5-hydroxyindoleacetic acid, a product of serotonin metabolism and the finding of decreased platelet aggregation after laser treatment.
There have been a variety of reported cellular effects following low-energy laser irradiation. These include stimulated collagen production and fibroblast activity, altered prostaglandin content, increased tissue activities of succinic dehydrogenase and lactic acid dehydrogenase, altered rates of DNA synthesis, cytoplasmic changes, and accelerated cellular proliferation.
In human studies, evaluations of wound healing in response to low-power laser treatment have found remarkable results for the healing of cervical erosions and a variety of skin ulcers. The studies, however, tend to be uncontrolled or incompletely described. In addition, other experiments that have involved swine with skin wounds have shown no benefit from laser treatment. Basford states: "It is important to remember that the literature on low-energy laser studies is uneven and disorganized. Future work may show that results now in apparent conflict are actually different aspects of the same problem."
Abergel et al., "Biostimulation of Wound Healing by Lasers: Experimental Approaches in Animal Models and in Fibroblast Cultures," Dermatol. Suro. Oncol. 13:1127-33, 1987, refer to a mechanism of action for collagen accumulation as a result of laser treatment. More specifically, Abergel et al. refer to the He-Ne laser as providing irradiation that might increase collagen production by fibroblasts via an enhancement of collagen gene expression on the transcriptional level. Enhancement of collagen accumulation could result from an elevation of collagen mRNA steady-state levels through an activation of the regulatory sequences of the corresponding genes.
A review of laser biostimulation (Enweneka, "Laser Biostimulation of Healing Wounds: Specific Effects and Mechanisms of Action," J. Orthopaedic Sports Phys and Therapy 9:333-38, 1988) refers to several proposed mechanisms of action, including suggestions that lasers:
1. Accelerate the inflammatory phase of wound healing by altering the levels of various prostaglandins, PA1 2. Increase ATP synthesis by enhancing electron transfer in the inner membrane of mitochondria, PA1 3. Accelerate protein (collagen) synthesis by accelerating DNA and RNA synthesis, PA1 4. Augment fibroplasia by a mechanism that is still being explored, and PA1 5. Enhance the ability of immune cells to combat invading pathogens.
Accordingly, it is known that low-power lasers have effects on wound healing, but it is still unclear as to the precise mechanism of action of the effects and how best to utilize laser irradiation to enhance or improve wound healing.
In separate and unrelated studies, it has been found that ascorbate is important in the regulation of collagen biosynthesis. The importance of ascorbic acid in the metabolism of connective tissues was realized as early as the sixteenth century. The explorer Jacques Cartier recognized that dietary intake, particularly of citrus fruits, was essential in preventing scurvy and treating those suffering from the disease.
Later studies showed the marked growth of embryonic chick bones grown in tissue culture media supplemented with ascorbic acid when compared to similar bones grown in media without ascorbic acid.
It later became known that ascorbic acid was an essential cofactor in the hydroxylation of proline and lysine to form hydroxyproline and hydroxylysine, amino acids essential to the formation of stable collagen. Hydroxyproline is necessary for collagen helix formation, and in its absence, collagen is unable to be properly secreted from fibroblasts Hydroxylysine is essential in collagen cross-link formation, and in its absence, the collagen would be structurally unstable.
Pinnell, "Regulation of Collagen Biosynthesis by Ascorbic Acid: A Review," Yale J. Biol. Med. 58:553-59, 1985, further demonstrated that ascorbic acid is a "fundamental signal for collagen production" which appears to be independent of its cofactor function for hydroxylation of proline and lysine.
Accordingly, it appears as though both low-power laser irradiation and exogenous administration of ascorbic acid can enhance wound healing by independent means. That is, the mechanisms of actions of both forms of wound healing treatment are independent of each other. Accordingly, there is a need in the art to determine the interrelationships of collagen synthesis and wound healing effects of low-power lasers and ascorbic acid. Furthermore, it is not known whether or not each mechanism of treatment of wound healing is acting independently, or if there is an interdependency that can lead to a synergistic combination.